Magnetic Resonance Imaging

BCMB/CHEM 8190

"for their discoveries concerning magnetic resonance imaging"

Paul C. Lauterbur Sir Peter Mansfield

The Nobel Prize in Physiology or Medicine 2003

Imaging System: 7T-210 mm

Imaging methods include

1. Relaxometric measurements (T1, T2

and T2* mapping)

2. Quantitative diffusion mapping (DWI)

and diffusion tensor imaging (DTI)

3. Quantization of vascular leakiness

and permeability of tumor tissue

4. Spectroscopic imaging of 1H

metabolites to monitor cellular

response to therapy

5. Blood flow measurements using ASL

(arterial spin labeling)

6. BOLD (blood oxygen level

dependent contrast) for fMRI

studies

RF coils are quite varied

• Transmit coils and gradient coils are often fixed

in the bore much like a high resolution system

• Observe coils may be localized on animal like

these surface coils

From Doty Scientific

Human MRI 3T: 60cm

UGA 3 Tesla magnet

Surface or volume coil

General Imaging System Components

(From Joy Hirsh, Columbia University)

Simple Imaging Strategy

• During gradient spins in each volume element have their

own precession frequency

• Can get a 1D image of sample – used in gradient shimming

High positive frequency

Zero frequency

High negative frequency

Z

Early Images Were Based on Tomography

Phantoms at particular regions of space give only signals at

frequencies corresponding to those regions. Gradients applied in

different directions can be combined for a 2(or 3)D image.

Simple 2D Image

• For 2D imaging use gradients in different directions (x, z)

in different evolution periods (t1, t2)

90x

Gz

Gx

t1 t2

z

x

1

2

Echo Planar Imaging – Speeding up Acquisitions

90x

Gz t2 t2 t2 t2 t2

t1

dw-1 dw-2 dw-3 dw-4 dw-5

• t2 will have spatial image (needs to be reversed in even dw)

• t1 can sample a number of different properties

• t1 could have a gradient in another dimension – 2D map

• t1 could sample chemical shift dispersion - MRSI

Slice Selection can be

combined with a 2D Image

• Strong gradients

make Larmor

frequencies different

at different positions.

• A long (often

shaped) RF pulse

only energizes slice

where field strength

matches Larmor

frequency.

Fie

ld S

trength

Z Position

12

8 M

hz

12

7 M

hz

12

6 M

hz

127 Mhz

RF pulse

Larmor

Freq

Data Processing

Fourier Transform in k Space

dkekSx kxi

2)()(

1. A simple circle at the center of the image

space and the representation of the circle

in k-space. Note that the k-space has the

greatest intensity at the center.

2. Additional of a second circle to the image

space introduces a grating pattern to the

k-space.

3. An image of the brain contains much

more spatial information, with much more

complex k-space representation

k(t) = t (dB/dx) dt’

for a time independent gradient

k(t) = const t

k can replace t in normal in t/ FT

to generate a space/reciprocal space FT

MR Contrast Agents

• In MRI, contrast agents are usually used to improve the

visibility of diseased tissues.

– T1 contrast: increase R1 relaxation rate, e.g.

Gadolinium (Gd), Mn2+

– T2 contrast: increase R2 rate, e.g. iron oxide

nanoparticles

– Chemical exchange saturation transfer (CEST):

nucleus exchanges between two or more chemical

environments

– Heteronuclear contrast: non-proton based, e.g. 19F,

129 Xe, or 13C

Mn2+ Enhanced MRI of Mouse Brain

• Figure 1. Typical horizontal (left), sagittal (center), and axial (right) cuts from a T1-weighted spin-echo 3D-MEMRI of a mouse brain. Resolution is approximately 100. 11.7T system. (Lee, Silva, Merkle, Koretsky, (2005) Mag. Res. In Med. 53, 640-648.

Contrast Agents based on Gd3+

Boutry et al., Magn. Reson. Med. 53: 800-807 (2005)

• Gd3+ is has

electron spin 7/2

• Shortens T1, T2

of water protons

• T1 weighted

image enhances

areas of binding

•This construct

targets areas of

inflammation

“Magnetic resonance imaging of cell surface receptors using targeted

contrast agents, D. Artemov, Z.M. Bhujwalla, J.W.M. Bulte, Current

Pharm. Biotech. 5:485-494.

Vascular Architecture can be Imaged

Figure 1. Rat hind-

quarters using a

contrast agent injected

Into the blood stream.

7T system.

(Varian website)

T2 Contrast agents

T2 contrast agent: increase R2 rate, e.g. iron oxide nanoparticles.

TEM images of Fe3O4, CoFe2O4, and MnFe2O4

Category

Nano-particles:

Mono-disperse (non-aggregated) iron oxide core (<20nm)

Ultra-small iron oxide:

Mono-disperse (<50nm)

Super-Paramagnetic Iron Oxide (SPIO)

Aggregated iron oxide core (>50nm)

Properties

Highly susceptible to magnetic fields and therefore easily magnetized

Applications: tracking/monitoring of labeled stem/tumor cells

Iron-Oxide R2s Depend on Bulk Susceptibilities

• All materials have a magnetic susceptibility,

• We can assign such a susceptibility to each volume element

• In the presence of a magnetic field each has an induced

dipole moment, B0 .

• Fields from these dipoles cancel in the interior of material,

but they do not at surfaces

• Hence shape dependent corrections

• Total field B = B0 [1 + (4/3 - ) ]

= -2 = 4/3

Quantification of iron concentration: T2* Relaxometry

• Can infer agent concentration from relaxation rates

• Basic premise is to observe the increase in relaxation rate with the Fe-based agent relaxivity known.

• Applies to T2 or T2*

• Experimental evidence shows relaxation rate is approximately linear at low concentration

CrRR Fe *

20

*

2

Picture adapted from Liu et al Magn Reson Med. 2009 Apr;61(4):761-6

Visualizing Implanted Stem Cells

These cells are labeled

with iron oxide nano-

particles and cells have

been injected into a mouse

heart. Data are from a 7T

MRI system.

(Kustermann et al. (2005)

NMRIn Biomedicine, 18,

362-370)

(MRSI)Magnetic Resonance

Spectroscopy Imaging

Prostate Cancer

B- Spectral Grid

C- MRSI Array

Swanson et al.

Cancer

Investigation

19, 510-523 (2001)

MRS in Monitoring Disease Progression:

a Mouse Model of Alzheimer’s Disease

Figure 1. Changes in brain metabolites as

a function of age. 9.4T study on 18L voxels.

Myoinositol is also seen in APP-PS1 mice.

(Marjanska,…, Ugurbil, Garwood, (2005) PNAS

102, 11906-11910.